Examination of the Oxidative Stress-Related Parameters with Methotrexate-Induced Albino Wistar Rats

In 1940s a specific antagonist for folic acid is developed for first time known as Methotrexate which inhibits the proliferation of malignant cells basically byinhibiting the de novo synthesis of purines and pyrimidines. The presented study concludes that the acute exposure to Methotrexate produced no appreciable changes but in routine consultation of oxidative stress parameters including the glutathione metabolizing system in patients using long term MTX cure can be considered. 

Methotrexate is a folic acid antagonist, widely used as a chemotherapeutic agent in the treatment of various cancerous stages (leukaemia, lymphoma, osteosarcoma, head and neck tumours, lung cancer, breast cancer, etc.) and in the treatment of various inflammatory diseases. It is also used for the treatment of multiple sclerosis,dermatomyositis, sarcoidosis, psoriasis, and rheumatoid arthritis, disorders causing inflammation. Its side effects include hypersensitivity pneumonia, central and peripheral nervous system toxicity, liver and gastrointestinal system dysfunctions and hematologic failure.

Need of Pharmacovigilance in AYUSH Drugs

Faculty of Pharmacy, Sri Ramachandra University in association with Society for Ethnopharmacology-Chennai chapter organized a National Seminar on “Pharmacovigilance of AYUSH drugs” on 19th January 2016, at Sri Ramachandra University. A session on need of pharmacovigilance in AYUSH drugs was discussed and the salient points are summarized.

In India, Ayurveda, Siddha and Unani (ASU) systems of medicine are considered to be the oldest system of medicines. They prescribe drugs of herbal, mineral, metallic and animal origin for the treatment of many diseases. Being time tested systems of medicine and majority of the drugs used by them are of herbal origin these systems are considered to be safe. The use of ASU medicines continues to expand rapidly across the world. The interest and demand for ASU system of medicine is day-by-day increasing both within India and abroad.

Efficacy or Exaggeration The Likely Role of Evefresh Cream for SLE

Personal care industries are aggressively competing and crowding the market with wide variety of sun screeners and SPF products to offer sun protection benefit to the customers.Photosensitivity is the major precursor of skin cancer. The global warming and increase in the solar coverage of earth has made different parts of our planet vulnerable to UV radiation. Further several occupational reasons have increased the solar exposure of people thus making them ‘risk group’ to sun.

Need of the hour is an effective sunlight protection of the skin more than SPF/UV preparations. The sunlight protection preparations in this article refer to products that would offer mild physical sun protection benefit (SPF 1 to 4) along with moisturisation and skin lightening effect. On the contrary SPF/UV preparations under reference are the preparations that have high SPF and contain multiple physical and chemical UV A and or B screeners.

Should Medications be Coadministered with Albumin in Hypoalbuminemic Patients

One of the factors that influence pharmacokinetic properties of drug distribution is protein binding. Medications that enter the body interact with tissue and plasma proteins. These interactions determine how the drug product will be distributed. Protein binding can be classified as irreversible and reversible. There are also varying degrees and percentages to which medications can be bound. Irreversible protein binding occurs when the drug and protein molecule bind tightly via covalent bonds. Reversible protein binding, the more common of the two, occurs via weaker hydrogen bonding or Van der Waals forces.

Protein binding is of great importance in pharmacokinetics and drug dosing due to the fact that protein bound drug is therapeutically unavailable for its intended action. It is only the unbound portion of the drug that is pharmacologically active. Thus, medications that are highly protein bound have a lower free fraction; the inverse relationship exists for minimally protein bound drugs.

Rethinking Demethylating Agents in Epigenetic Cancer Therapy

Our understanding of how to use DNA methyltransferase (DNMT) inhibitors to target DNA methylation in cancer therapy have come a long way since the nucleotide analogs 5-Azacytidine (5-Aza-CR, Vidaza) and 5-Aza-2’-deoxycytidine (5-Aza-2-CdR, Decitabine) were approved by the FDA over a decade ago for the treatment of myeloid dysplastic syndrome. First developed as chemotherapeutic agents, these compounds (hereon referred collectively as AZA) were found to reduce DNA methylation level in tumor cells, thus acting as demethylating agents. DNA methylation is a covalent addition of a methyl group at the fifth carbon of cytosines that are present in the context of CpG dinucleotides. DNA methylation is a component of epigenetic machineries, which in normal cells, is critical for silencing of retrotransposons, and during genomic silencing and X-inactivation. Although the levels may vary, global changes in DNA methylation have been shown to be a key feature of cancer cells. Furthermore, DNA methylation is dynamic and pharmacologically reversible and thus, an attractive target for cancer therapy.

 

Decades of study have shown that while cancer cells exhibit global decrease in DNA methylation, there are punctate regions throughout the genome that have markedly increased DNA methylation level. This hypermethylation pattern is strongly associated with the silencing of genes, including tumor suppressor genes, leading to gene expression profile that favor uncontrollable cell growth.

Probabilistic Analysis: Sensitivity Analysis or Main Result?

According to virtually all published Pharmacoeconomics guidelines, the base case analyses (understood as the main result) must be deterministic. That is, the main result of an economic model (the incremental cost-effectiveness ratio, ICER) is a fixed result and is not subject to any uncertainty analysis. For example, with deterministic base case analysis we can obtain an ICER of 10,000 € per QALY gained with a new drug versus the former, but we do not know what confidence can we accept this result and what is the likelihood that the drug is cost-effective for a certain willingness to pay. The one-way sensitivity analysis, usually presented as tornado diagram is a deterministic analysis very useful to determine which variables of the study drivers of the result are obtained in the base case. 

According to the NICE guidelines "wherever possible the results of the economic comparisons should be subjected to sensitivity analysis testing. For example, when data are drawn exclusively from clinical trials, 95% confidence intervals can be calculated for cost-effectiveness ratios. When data are drawn from a variety of sources and used in a modelling framework, probabilistic sensitivity analysis is recommended in order to take account of the uncertainty around data values". According to the ISPOR guidelines "for model-based economic evaluations, parameter uncertainty may be represented for individual parameters in a deterministic sensitivity analysis or across all parameters simultaneously with probabilistic analysis".

Antimicrobial Activity of Flavone Analogues

Flavonoids are a group of natural compounds having a benzo-pyrone ring, and over 4,000 flavonoid compounds have been characterized and classified according to chemical structure. Available reports tend to show that secondary metabolitesof phenolic nature, including flavonoids are responsible for the variety ofpharmacological activities . Their activities are structure dependent. The chemical nature of flavonoids depends on their structural class, degree of hydroxylation, reduction, other substitutions, conjugations, and degree of polymerization. Flavonoids are widely present in the plant kingdom exhibiting a broad range of biological activities, including antibacterial, antifungal, antiviral, anti-allergic, anti-inflammatory, and anti-proliferative and antioxidant activities. 

 

It has been reported that the intensity of the antimicrobial activity of a flavonoid strongly depends on its chemical structure, which is particularly influenced by the number and position of various functional groups such as, hydroxyl, methoxy, halogens, nitro, methyl, cyano groups attached to the two aromatic rings (A and B). The third ring C islinked through a three carbon chain, mostly organized as an oxygenatedheterocyclic ring. A very few reports are available to the substitution pattern in ring C at 3-position. However 3-hydroxy flavones and 3-methyl flavones have been synthesized by many researchers, but their further reductions at 2,3-position in ring C are rare and yet to be explored. Substitution pattern at 3-position of ring C mainly regulates bioavailability and metabolism. Whereas substitution at ring A and B influence biological activity. Flavonoids are well known as antibacterial agents against a wide range of pathogenic microorganism.